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<title>07 February, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies</strong> -
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<div>
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SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.05.527215v1" target="_blank">Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies</a>
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</div></li>
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<li><strong>Disease severity of unvaccinated SARS-CoV-2 positive adults less than 65 years old without comorbidity, in the Omicron period and pre-Omicron periods</strong> -
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Background: The reduced severity and burden of COVID-19 in 2022 can largely be attributable to vaccination and a shift to Omicron predominance. However, millions of individuals remain unvaccinated. In the present study, we aimed to study disease severity in unvaccinated individuals without risk factors during the Omicron period, compared to pre-Omicron periods. Methods: This register-based study included all unvaccinated individuals in Sweden aged 18-64 years without comorbidity or care dependency who were SARS-CoV-2 positive between week 45 of 2020 and week 5 of 2022. Variant of concern (VOC) periods were periods with certain VOCs identified in ≥92% of sequenced cases nationwide. Outcomes were hospitalization with a main discharge code of COVID-19; severe illness, defined as high-flow nasal oxygen treatment or intensive care unit admission; and death with COVID-19 as the underlying cause of death on the death certificate. Results: Among 788,895 individuals in the overall SARS-CoV-2 positive cohort, both hospitalization and death increased stepwise from the pre-VOC period to the Alpha and Delta periods, and decreased in the Omicron period. Among 15,179 patients hospitalized for COVID-19, the proportions with severe illness and death increased to the Delta period, but in the Omicron period, these outcomes returned to the level of the pre-VOC period. Conclusion: In the Omicron period, compared to pre-Omicron periods, unvaccinated SARS-CoV-2 positive adults <65 years old without comorbidity had reduced proportions of hospitalization and death overall, but similar proportion of severe illness among patients hospitalized for COVID-19. These results support continuous efforts to prevent hospitalizations for COVID-19.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.02.23285377v1" target="_blank">Disease severity of unvaccinated SARS-CoV-2 positive adults less than 65 years old without comorbidity, in the Omicron period and pre-Omicron periods</a>
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</div></li>
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<li><strong>A Rapid review on the COVID-19 Pandemic’s Global Impact on Breast Cancer Screening Participation Rates and Volumes from January-December 2020</strong> -
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Background: COVID-19 has strained population breast mammography screening programs that aim to diagnose and treat breast cancers earlier. As the pandemic has affected countries differently, we aimed to quantify changes in breast screening volume and uptake during the first year of the COVID-19 pandemic. Methods: We systematically searched Medline, the WHO (World Health Organization) COVID-19 database, and governmental databases. Studies covering January 2020 to March 2022 were included. We extracted and analyzed data regarding study methodology, screening volume and uptake. To assess for risk-of bias, we used the Joanna Briggs Institute Critical Appraisal tool. Results: Twenty-six cross-sectional descriptive studies were included out of 935 independent records. Reductions in screening volume and uptake rates were observed among eight countries. Changes in screening participation volume in five countries with national population-based screening ranged from -13% to –31%. Among two countries with limited population-based programs the decline ranged from -61% to -41%. Within the USA, population participation volumes varied ranging from +18% to -39% with suggestion of differences by insurance status (HMO, Medicare, and low-income programs). Almost all studies had high risk-of-bias due to insufficient statistical analysis and confounding factors. Discussion and Conclusion: Extent of COVID-19-induced reduction in breast screening participation volume differed by region and data suggested potential differences by healthcare setting (e.g., national health insurance vs private health care). Recovery efforts should monitor access to screening and early diagnosis to determine if prevention services need strengthening to increase coverage of marginalized groups and reduce disparities.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.06.23285513v1" target="_blank">A Rapid review on the COVID-19 Pandemic’s Global Impact on Breast Cancer Screening Participation Rates and Volumes from January-December 2020</a>
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</div></li>
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<li><strong>Taxonomical and ontological analysis of verified natural and laboratory human coronavirus hosts</strong> -
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<div>
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To fully understand COVID-19, it is critical to identify and analyze all the possible hosts of SARS-CoV-2 (the pathogen of COVID-19) and compare them with the hosts of other human coronaviruses. In this study, we collected, annotated, and performed taxonomical and ontological analysis of all the reported and verified hosts for all human coronaviruses including SARS-CoV, MERS-CoV, SARS-CoV-2, and four others that cause the common cold. A total of 37 natural hosts and 19 laboratory animal hosts of host human coronaviruses were identified based on experimental or clinical evidence. Our taxonomical ontology-based analysis found that all the verified susceptible natural and laboratory animals belong to therian mammals. Specifically, these 37 natural therian hosts include one wildlife marsupial mammal (i.e., Didelphis virginiana) and 36 Eutheria mammals (a.k.a. placental mammals). The 19 laboratory animal hosts are also classified as placental mammals. While several non-therian animals (including snake, housefly, zebrafish) were reported to be likely SARS-CoV-2 hosts, our analysis excluded them due to the lack of convincing evidence. Genetically modified mouse models with human Angiotensin-converting enzyme 2 (ACE2) or dipeptidyl peptidase-4 (DPP4) protein were more susceptible to virulent human coronaviruses with clear symptoms. Coronaviruses often became more virulent and adaptive in the mouse hosts after a series of viral passages in the mice. To support knowledge standardization and analysis, we have also represented the annotated host knowledge in the Coronavirus Infectious Disease Ontology (CIDO) and provided ways to automatically query the knowledge.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.05.527173v1" target="_blank">Taxonomical and ontological analysis of verified natural and laboratory human coronavirus hosts</a>
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</div></li>
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<li><strong>S373P Mutation Stabilizes the Receptor-binding Domain of Spike Protein in Omicron and Promotes Binding</strong> -
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<div>
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Recently, a cluster of several newly occurring mutations on Omicron, which is currently the dominant SARS-CoV-2 variant, are found at the (mechanically) stable {beta}-core region of spike proteins receptor-binding domain (RBD), where mutation rarely happened before. Notably, the binding of SARS-CoV-2 to human receptor ACE2 via RBD happens in a dynamic airway environment, where mechanical force caused by coughing or sneezing occurs and applies to the proteins. Thus, we used atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) to measure the stability of RBDs and found that the unfolding force of Omicron RBD increased by 20% compared with the wild-type. Molecular dynamics simulations revealed that Omicron RBD showed more hydrogen bonds in the {beta}-core region due to the closing of the -helical motif caused primarily by the S373P mutation, which was further confirmed by the experiment. This work reveals the stabilizing effect of the S373P mutation and suggests mechanical stability becomes another important factor in SARS-CoV-2 mutation selection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.22.497114v3" target="_blank">S373P Mutation Stabilizes the Receptor-binding Domain of Spike Protein in Omicron and Promotes Binding</a>
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</div></li>
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<li><strong>Low Density Lipoprotein Receptor-Related Protein 1 (LRP1) as an auxiliary host factor for RNA viruses including SARS-CoV-2</strong> -
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<div>
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Viruses with an RNA genome are often the cause of zoonotic infections. In order to identify novel pro-viral host cell factors, we screened a haploid insertion-mutagenized mouse embryonic cell library for clones that rendered them resistant to the zoonotic Rift Valley fever virus (RVFV; family Phleboviridae, order Bunyavirales). This screen returned the Low Density Lipoprotein Receptor-Related protein 1 (LRP1, or CD91) as top hit, a 600 kDa plasma membrane protein known to be involved in a wide variety of cell activities. Inactivation of LRP1 expression in human cells reduced RVFV RNA levels already at the attachment and entry stages of infection. Moreover, the role of LRP1 in promoting RVFV infection was dependent on physiological levels of cholesterol and on endocytosis. In the highly LRP1-positive human cell line HuH-7, LRP1 also promoted the early infection stages of Sandfly fever Sicilian virus (SFSV; family Phleboviridae, order Bunyavirales), La Crosse virus (LACV; family Peribunyaviridae, order Bunyavirales), had a minor effect on RNA levels during the late infection stages by vesicular stomatitis virus (VSV; family Rhabdoviridae, order Mononegavirales), whereas infection by Encephalomyocarditis virus (EMCV, family Picornaviridae) was entirely LRP1-independent. Moreover, siRNA experoments in human Calu-3 cells demonstrated that also SARS-CoV-2 infection benefitted from LRP1. Thus, we identified LRP1 as a host factor that supports infection by a spectrum of RNA viruses.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.17.480904v2" target="_blank">Low Density Lipoprotein Receptor-Related Protein 1 (LRP1) as an auxiliary host factor for RNA viruses including SARS-CoV-2</a>
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</div></li>
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<li><strong>Blue uncertainty: Warding off systemic risks in the Anthropocene – Lessons from COVID-19</strong> -
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COVID-19 has made evident the complex interdependence of social and ecological systems and that to reduce the risk of future zoonotic pandemics we must safeguard nature. Approaches based on complexity science taking into account that interdependence and its associated systemic risks must be mainstreamed in current policy making, in general. However, at present, that could result in failure for three main reasons: (1) those approaches might be too sophisticated for current policy making pursuing sustainable development; (2) the reductionist views from conventional economics still deeply influence economic and environmental policy making; (3) it is unlikely that far-reaching policies aimed at stimulating post-pandemic economic development can be steered through radically innovative approaches that remain untested. Here, using COVID-19 as an example, I suggest that the use of innovative complexity-based approaches could be enabled through intermediary approaches equipped to resonate with the mindset pervading current policy making.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/z2br5/" target="_blank">Blue uncertainty: Warding off systemic risks in the Anthropocene – Lessons from COVID-19</a>
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<li><strong>Over- and under-estimation of vaccine effectiveness</strong> -
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Background: The effectiveness of SARS-CoV-2 vaccines has been a subject of debate, with varying results reported in different studies, ranging from 60-95% vaccine effectiveness (VE). This range is striking when comparing two studies conducted in Israel at the same time, as one study reported VE of 90-95%, while the other study reported only ~80%. We argue that this variability is due to inadequate accounting for indirect protection provided by vaccines, which can block further transmission of the virus Materials and Methods: We developed a novel analytic heterogenous infection model and extended our agent-based model of disease spread to allow for heterogenous interactions between vaccinated and unvaccinated across close-contacts and regions. We applied these models on real-world regional data from Israel from early 2021 to estimate VE using two common study designs: population-based and secondary infections Results: Our results show that the estimated VE of a vaccine with efficacy of 85% can range from 70-95% depending on the interactions between vaccinated and unvaccinated individuals. Since different study designs capture different levels of interactions, we suggest that this interference explains the variability across studies. Finally, we propose a methodology for more accurate estimation without knowledge of interactions Discussions and Conclusions: Our study highlights the importance of considering indirect protection when estimating vaccine effectiveness, explains how different study designs may report biased estimations, and propose a method to overcome this bias. We hope that our models will lead to more accurate understanding of the impact of vaccinations and inform public health policy.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.24.22269737v2" target="_blank">Over- and under-estimation of vaccine effectiveness</a>
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</div></li>
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<li><strong>Development of interoperable, domain-specific extensions for the German Corona Consensus (GECCO) COVID-19 research dataset using an interdisciplinary, consensus-based workflow</strong> -
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<b>Background</b> The COVID-19 pandemic has spurred large-scale, inter-institutional research efforts. To enable these efforts, researchers must agree on dataset definitions that not only cover all elements relevant to the respective medical specialty but that are also syntactically and semantically interoperable. Following such an effort, the German Corona Consensus (GECCO) dataset has been developed previously as a harmonized, interoperable collection of the most relevant data elements for COVID-19-related patient research. As GECCO has been developed as a compact core dataset across all medical fields, the focused research within particular medical domains demands the definition of extension modules that include those data elements that are most relevant to the research performed in these individual medical specialties. <b>Objective</b> To (i) specify a workflow for the development of interoperable dataset definitions that involves a close collaboration between medical experts and information scientists and to (ii) apply the workflow to develop dataset definitions that include data elements most relevant to COVID-19-related patient research in immunization, pediatrics, and cardiology. <b>Methods</b> We developed a workflow to create dataset definitions that are (i) content-wise as relevant as possible to a specific field of study and (ii) universally usable across computer systems, institutions, and countries, i.e., interoperable. We then gathered medical experts from three specialties (immunization, pediatrics, and cardiology) to the select data elements most relevant to COVID-19-related patient research in the respective specialty. We mapped the data elements to international standardized vocabularies and created data exchange specifications using HL7 FHIR. All steps were performed in close interdisciplinary collaboration between medical domain experts and medical information scientists. The profiles and vocabulary mappings were syntactically and semantically validated in a two-stage process. <b>Results</b> We created GECCO extension modules for the immunization, pediatrics, and cardiology domains with respect to the pandemic requests. The data elements included in each of these modules were selected according to the here developed consensus-based workflow by medical experts from the respective specialty to ensure that the contents are aligned with the respective research needs. We defined dataset specifications for a total number of 48 (immunization), 150 (pediatrics), and 52 (cardiology) data elements that complement the GECCO core dataset. We created and published implementation guides and example implementations as well as dataset annotations for each extension module. <b>Conclusions</b> These here presented GECCO extension modules, which contain data elements most relevant to COVID-19-related patient research in immunization, pediatrics and cardiology, were defined in an interdisciplinary, iterative, consensus-based workflow that may serve as a blueprint for the development of further dataset definitions. The GECCO extension modules provide a standardized and harmonized definition of specialty-related datasets that can help to enable inter-institutional and cross-country COVID-19 research in these specialties.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.12.22274089v2" target="_blank">Development of interoperable, domain-specific extensions for the German Corona Consensus (GECCO) COVID-19 research dataset using an interdisciplinary, consensus-based workflow</a>
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</div></li>
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<li><strong>Acoustic and perceptual impact of face masks on speech: A scoping review</strong> -
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During the COVID-19 pandemic, personal protective equipment such as facial masks and coverings were mandated all over the globe to protect against the virus. Although the primary aim of wearing face masks is to protect against viral transmission, they pose a potential burden on communication. The purpose of this scoping review was to identify the state of the evidence of the effect of facial coverings on acoustic and perceptual speech outcomes. The scoping review followed the framework created by Arksey & O’Malley (2005) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines (PRISMA-ScR; Tricco et al., 2018). The search was completed in May 2021 across the following databases: PubMed, EMBASE, PsycINFO, Web of Science, and Google Scholar. A total of 3,846 records were retrieved from the database search. Following the removal of duplicates, 3,479 remained for the title/abstract screen and 149 were selected for the full-text review. Of these, 52 were included in the final review and relevant data were extracted. The 52 articles included in the final review consisted of; 11 studied perceptual outcomes only, 16 studied acoustic outcomes only, and 14 studied both perceptual and acoustic outcomes. 13 of these investigated acoustic features that could be used for mask classification. Although the findings varied from article to article, many trends stood out. Many articles revealed that face masks act as a low pass filter, dampening sounds at higher frequencies; however, the frequency range and the degree of attenuation varied based on face mask type. All but five articles that reported on perceptual outcomes showed a common trend that wearing a face mask was associated with poorer speech intelligibility. The findings of the scoping review provided evidence that facial coverings negatively impacted speech intelligibility, which is likely due to a combination of auditory and visual cue degradation. Due to the continued prevalence of mask use, how facial coverings affect a wider variety of speaker populations, such as those with communication impairments, and strategies for overcoming communication challenges should be explored.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/fpsu2/" target="_blank">Acoustic and perceptual impact of face masks on speech: A scoping review</a>
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</div></li>
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<li><strong>Automated Agnostic Designation of Pathogen Lineages</strong> -
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Pathogen nomenclature systems are a key component of effective communication and collaboration for researchers and public health workers. Since February 2021, the Pango nomenclature for SARS-CoV-2 has been sustained by crowdsourced lineage proposals as new isolates were added to a growing global dataset. This approach to dynamic lineage designation is dependent on a large and active epidemiological community identifying and curating each new lineage. This is vulnerable to time-critical delays as well as regional and personal bias. To address these issues, we developed a simple heuristic approach that divides a phylogenetic tree into lineages based on shared ancestral genotypes. We additionally provide a framework that automatically prioritizes the lineages by growth rate and association with key mutations or locations, extensible to any pathogen. Our implementation is efficient on extremely large phylogenetic trees and produces similar results to existing Pango lineage designations when applied to SARS-CoV-2. This method offers a simple, automated and consistent approach to pathogen nomenclature that can assist researchers in developing and maintaining phylogeny-based classifications in the face of ever increasing genomic datasets.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.03.527052v1" target="_blank">Automated Agnostic Designation of Pathogen Lineages</a>
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<li><strong>Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C)</strong> -
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Importance: Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management. Objective: To examine, using data from the National COVID Cohort Collaborative (N3C), whether patients with pre-existing autoimmune disease (AID) diagnosis and/or immunosuppressant (IS) exposure are at a higher risk of developing severe COVID-19 outcomes. Design, setting and participants: A retrospective cohort of 2,453,799 individuals diagnosed with COVID-19 between January 1st, 2020, and June 30th, 2022, was created from the N3C data enclave, which comprises data of 15,231,849 patients from 75 USA data partners. Patients were stratified as those with/without a pre-existing diagnosis of AID and/or those with/without exposure to IS prior to COVID-19. Main outcomes and measures: Two outcomes of COVID-19 severity, derived from the World Health Organization severity score, were defined, namely life-threatening disease and hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression models with and without adjustment for demographics (age, BMI, gender, race, ethnicity, smoking status), and comorbidities (cardiovascular disease, dementia, pulmonary disease, liver disease, type 2 diabetes mellitus, kidney disease, cancer, and HIV infection). Results: In total, 2,453,799 (16.11% of the N3C cohort) adults (age> 18 years) were diagnosed with COVID-19, of which 191,520 (7.81%) had a prior AID diagnosis, and 278,095 (11.33%) had a prior IS exposure. Logistic regression models adjusted for demographic factors and comorbidities demonstrated that individuals with a prior AID (OR = 1.13, 95% CI 1.09 - 1.17; p=2.43E-13), prior exposure to IS (OR= 1.27, 95% CI 1.24 - 1.30; p=3.66E-74), or both (OR= 1.35, 95% CI 1.29 - 1.40; p=7.50E-49) were more likely to have a life-threatening COVID-19 disease. These results were confirmed after adjusting for exposure to antivirals and vaccination in a cohort subset with COVID-19 diagnosis dates after December 2021 (AID OR = 1.18, 95% CI 1.02 - 1.36; p=2.46E-02; IS OR= 1.60, 95% CI 1.41 - 1.80; p=5.11E-14; AID+IS OR= 1.93, 95% CI 1.62 - 2.30; p=1.68E-13). These results were consistent when evaluating hospitalization as the outcome and also when stratifying by race and sex. Finally, a sensitivity analysis evaluating specific IS revealed that TNF inhibitors were protective against life-threatening disease (OR = 0.80, 95% CI 0.66- 0.96; p=1.66E-2) and hospitalization (OR = 0.80, 95% CI 0.73 - 0.89; p=1.06E-05). Conclusions and Relevance: Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.02.23285353v1" target="_blank">Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C)</a>
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</div></li>
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<li><strong>Epidemic patterns of emerging variants with dynamical social distancing</strong> -
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Motivated by the emergence of new variants during the COVID-19 pandemic, we consider an epidemiological model of disease transmission dynamics, where novel strains appear by mutations of the virus. In the considered scenarios, disease prevalence in the population is modulated by social distancing. We study the various patterns that are generated under different assumptions of cross-immunity. If recovery from a given strain provides immunity against all previous strains, but not against more novel strains, then we observe a very regular sequential pattern of strain replacement where newer strains predominate over older strains. However, if protection upon recovery holds only against that particular strain and none of the others, we find much more complicated dynamics with potential recurrence of earlier strains, and co-circulation of various strains. We compare the observed patterns with genomic analysis we have seen during the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.03.526970v1" target="_blank">Epidemic patterns of emerging variants with dynamical social distancing</a>
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<li><strong>Omicron’s Intrinsic Gene-Gene Interactions Jumped Away from Earlier SARS-CoV-2 Variants and Gene Homologs between Humans and Animals</strong> -
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Omicron and its subvariants have become the predominant SARS-CoV-2 variants worldwide. The Omicron’s basic reproduction number (R0) has been close to 20 or higher. However, it is not known what caused such an extremely high R0. This work aims to find an explanation for such high R0 Omicron infection. We found that Omicron’s intrinsic gene-gene interactions jumped away from earlier SARS-CoV-2 variants which can be fully described by a miniature set of genes reported in our earlier work. We found that the gene PTAFR (Platelet Activating Factor Receptor) is highly correlated with Omicron variants, and so is the gene CCNI (Cyclin I), which is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog. The combination of PTAFR and CCNI can lead to a 100% accuracy of differentiating Omicron COVID-19 infection and COVID-19 negative. We hypothesize that Omicron variants were potentially jumped from COVID-19-infected animals back to humans. In addition, there are also several other two-gene interactions that lead to 100% accuracy. Such observations can explain Omicron’s fast-spread reproduction capability as either of those two-gene interactions can lead to COVID-19 infection, i.e., multiplication of R0s leads to a much higher R0. At the genomic level, PTAFR, CCNI, and several other genes identified in this work rise to Omicron druggable targets and antiviral drugs besides the existing antiviral drugs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.01.526736v1" target="_blank">Omicron’s Intrinsic Gene-Gene Interactions Jumped Away from Earlier SARS-CoV-2 Variants and Gene Homologs between Humans and Animals</a>
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<li><strong>Data-driven User Model Development of a Conversational AI Chatbot to provide Assistance to Unemployed People during the COVID-19 Pandemic</strong> -
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The COVID-19 pandemic triggered lockdowns all over the world, leading to unprecedented job losses. In the US, this resulted in many first time unemployment benefits filers struggled to navigate the benefits information provided by federal and state websites. We developed BEBO (Benefits Bot) to address these pain points and to provide appropriate and timely information. This paper explains the data-driven user model that was developed to create a user-centric conversational AI chatbot.
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🖺 Full Text HTML: <a href="https://osf.io/thqf5/" target="_blank">Data-driven User Model Development of a Conversational AI Chatbot to provide Assistance to Unemployed People during the COVID-19 Pandemic</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br/><b>Sponsors</b>: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Plitidepsin<br/><b>Sponsor</b>: PharmaMar<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Corfluvec component 1 low dose; Biological: Corfluvec component 2 low dose; Biological: Corfluvec component 1 high dose; Biological: Corfluvec component 2 high dose; Biological: Corfluvec low dose; Biological: Corfluvec high dose; Biological: Placebo<br/><b>Sponsors</b>: Tatyana Zubkova; MDP-CRO, LLC; St. Petersburg State Pavlov Medical University<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Self-testing Study</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: SMARTest mobile app for COVID-19 self-testing<br/><b>Sponsor</b>: Columbia University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Nirmatrelvir-Ritonavir<br/><b>Sponsors</b>: Shandong Provincial Hospital; Central hospital Affiliated to Shandong First Medical University; The Second Affiliated Hospital of Shandong First Medical University; The Affiliated Hospital Of Southwest Medical University; Gansu Provincial Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tetrandrine Tablets Used in Hospitalized Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Tetrandrine<br/><b>Sponsor</b>: Peking University Third Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: HIGH FREQUENCY CHEST WALL OSCILLATION<br/><b>Sponsor</b>: Cairo University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120 nasal spray; Drug: Placebo Comparator<br/><b>Sponsor</b>: Huahui Health<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: VV116+SOC; Drug: SOC<br/><b>Sponsor</b>: Chengdu Zenitar Biomedical Technology Co., Ltd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pirfenidone in Adult Hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Pirfenidone Oral Product; Drug: Pirfenidone placebo<br/><b>Sponsor</b>: Capital Medical University<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Non-invasive Ventilation<br/><b>Interventions</b>: Device: Non-invasive high-frequency oscillatory ventilation; Device: Non-invasive continuous positive airway pressure ventilation<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Molecular OTC At Home Test</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Diagnostic Test: Diagnostic Test: IN Vitro<br/><b>Sponsor</b>: 3EO Health<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Randomized-controlled Trial of Immunoadsorption (IA) in Patients With Chronic Fatigue Syndrome (CFS) Including Patients With Post-COVID-19 CFS (PACS-CFS)</strong> - <b>Condition</b>: ME/CSF Including CFS Related to Post-acute COVID-19 Syndrome (PACS)<br/><b>Intervention</b>: Device: Immunoadsorption<br/><b>Sponsor</b>: Charite University, Berlin, Germany<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II/III Immunogenicity and Safety Study of the AVX/COVID-12 Vaccine Against COVID-19 Applied as a Booster.</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: AVX-COVID/12; Biological: ChAdOx-1-S[recombinant]<br/><b>Sponsors</b>: Laboratorio Avi-Mex, S.A. de C.V.; National Council of Science and Technology, Mexico; Instituto Nacional de Enfermedades Respiratorias<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Brain-Training Treatment for Long COVID in Older Adults</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: NeuroFlex (computerized gamified tasks)<br/><b>Sponsor</b>: UConn Health<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Detection of IgM, IgG, IgA and neutralizing antibody responses to SARS-CoV-2 infection and mRNA vaccination</strong> - Introduction. One correlate of immunity for coronavirus disease 2019 (COVID-19) is the laboratory detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. These tests are widely implemented for clinical, public health, or research uses.Hypothesis/Gap Statement. Antibody responses by all classes of immunoglobulins may form from infection and vaccination, but few studies have performed direct head-to-head comparisons between these groups.Aim. The objective of this…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 nucleocapsid protein-RNA interaction by guanosine oligomeric RNA</strong> - The interaction of the β-coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein with genomic RNA is initiated by specific RNA regions and subsequently induces the formation of a continuous polymer with characteristic structural units for viral formation. We hypothesized that oligomeric RNAs, whose sequences are absent in the 29.9-kb genome sequence of SARS-CoV-2, might affect RNA-N protein interactions. We identified two such hexameric RNAs, In-1…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2</strong> - LY6E is an antiviral protein that inhibits coronavirus entry. Its expression in immune cells allows mice to control murine coronavirus infection. However, it is not known which immune cell subsets mediate this control or whether LY6E protects mice from SARS-CoV-2. In this study, we used tissue-specific Cre recombinase expression to ablate Ly6e in distinct immune compartments or in all epiblast-derived cells, and bone marrow chimeras to target Ly6e in a subset of radioresistant cells. Mice…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Vitamin D and estrogen steroid hormones and their immunogenetic roles in Infectious respiratory (TB and COVID-19) diseases</strong> - The role of steroid hormones against infectious diseases has been extensively studied. From immunomodulatory action to direct inhibition of microorganism growth, hormones D3 (VD3) and 17β-estradiol (E2), and the genetic pathways modulated by them, are key targets for a better understanding pathogenesis of infectious respiratory diseases (IRD) such as tuberculosis (TB) and the coronavirus disease-19 (COVID-19). Currently, the world faces two major public health problems, the outbreak of COVID-19,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cell-autonomous requirement for ACE2 across organs in lethal mouse SARS-CoV-2 infection</strong> - Angiotensin-converting enzyme 2 (ACE2) is the cell-surface receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). While its central role in Coronavirus Disease 2019 (COVID-19) pathogenesis is indisputable, there remains significant debate regarding the role of this transmembrane carboxypeptidase in the disease course. These include the role of soluble versus membrane-bound ACE2, as well as ACE2-independent mechanisms that may contribute to viral spread. Testing these roles…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DDX3X Is Hijacked by Snakehead Vesiculovirus Phosphoprotein To Facilitate Virus Replication via Stabilization of the Phosphoprotein</strong> - Asp-Glu-Ala-Asp (DEAD) box helicase 3 X-linked (DDX3X) plays important regulatory roles in the replication of many viruses. However, the role of DDX3X in rhabdovirus replication has seldomly been investigated. In this study, snakehead vesiculovirus (SHVV), a kind of fish rhabdovirus, was used to study the role of DDX3X in rhabdovirus replication. DDX3X was identified as an interacting partner of SHVV phosphoprotein (P). The expression level of DDX3X was increased at an early stage of SHVV…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CRISPR-Cas13d effectively targets SARS-CoV-2 variants, including Delta and Omicron, and inhibits viral infection</strong> - The recent pandemic of variants of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for innovative anti-SARS-CoV-2 approaches in addition to vaccines and antiviral therapeutics. Here, we demonstrate that a CRISPR-Cas13-based strategy against SARS-CoV-2 can effectively degrade viral RNA. First, we conducted a cytological infection experiment, screened CRISPR-associated RNAs (crRNAs) targeting conserved regions of viruses, and used an in vitro…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Intelligent ABM-based Framework for Developing Pandemic-Resilient Urban Spaces in Post-COVID Smart Cities</strong> - As of August 2022, the COVID-19 pandemic has accounted for over six million deaths globally. The urban population has been severely affected by this viral pandemic and the ensuing lockdowns, resulting in increased poverty and inequality, slowed economic growth, and a general decline in quality of life. This paper proposes a framework to evaluate the effects of the pandemic by combining agent-based simulations-based on Susceptible-Infectious-Recovered (SIR) model-with a hybrid neural network. A…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Severe acute respiratory syndrome coronavirus 2 may cause liver injury <em>via</em> Na<sup>+</sup>/H<sup>+</sup> exchanger</strong> - The liver has many significant functions, such as detoxification, the urea cycle, gluconeogenesis, and protein synthesis. Systemic diseases, hypoxia, infections, drugs, and toxins can easily affect the liver, which is extremely sensitive to injury. Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage. The primary regulator of intracellular pH in the liver is the Na<sup>(+)/H</sup>(+) exchanger (NHE). Physiologically, NHE protects hepatocytes from apoptosis by…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Age-adjusted impact of prior COVID-19 on SARS-CoV-2 mRNA vaccine response</strong> - More people with a history of prior infection are receiving SARS-CoV-2 vaccines. Understanding the level of protection granted by ‘hybrid immunity’, the combined response of infection- and vaccine-induced immunity, may impact vaccination strategies through tailored dosing. A total of 36 infected (‘prior infection’) and 33 SARS-CoV-2 ‘naïve’ individuals participated. Participants provided sera six months after completing a round of BNT162b2 vaccination, to be processed for anti-spike antibody…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The possible therapeutic role of curcumin and quercetin in the <em>early-stage</em> of COVID-19-Results from a pragmatic randomized clinical trial</strong> - CONCLUSION: The results revealed in this exploratory study suggest a possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19. It is proposed that the two agents possibly acting in synergy, interfere the SARS-CoV-2 replication, and thus help a speedy recovery in the early-stage of COVID-19. Further research is highly encouraged.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Enantioselective inhibition of the SARS-CoV-2 main protease with rhenium(i) picolinic acid complexes</strong> - Infections of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have triggered a global pandemic with millions of deaths worldwide. Herein, the synthesis of functionalized Re(i) tricarbonyl complexes as inhibitors of the SARS-CoV-2 main protease, also referred to as the 3-chymotrypsin-like protease (3CL^(pro)), is presented. The metal complexes were found to inhibit the activity of the enzyme with IC(50) values in the low micromolar range. Mass spectrometry revealed that the metal…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Studies of cytotoxicity effects, SARS-CoV-2 main protease inhibition, and in silico interactions of synthetic chalcones</strong> - SARS-CoV-2 main protease (Mpro) plays an essential role in proteolysis cleavage that promotes coronavirus replication. Thus, attenuating the activity of this enzyme represents a strategy to develop antiviral agents. We report inhibitory effects against Mpro of 40 synthetic chalcones, and cytotoxicity activities, hemolysis, and in silico interactions of active compounds. Seven of them bearing a (E)-3-(furan-2-yl)-1-arylprop-2-en-1-one skeleton (10, 28, and 35-39) showed enzyme inhibition with…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nucleolin mediates SARS-CoV-2 replication and viral-induced apoptosis of host cells</strong> - Host-oriented antiviral therapeutics are promising treatment options to combat COVID-19 and its emerging variants. However, relatively little is known about the cellular proteins hijacked by SARS-CoV-2 for its replication. Here we show that SARS-CoV-2 induces expression and cytoplasmic translocation of the nucleolar protein, nucleolin (NCL). NCL interacts with SARS-CoV-2 viral proteins and co-localizes with N-protein in the nucleolus and in stress granules. Knockdown of NCL decreases the stress…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>JAK-STAT inhibition reduces endothelial pro-thrombotic activation and leukocyte- endothelial pro-adhesive interactions</strong> - BACKGROUND: Vascular activation is characterized by increased pro-inflammatory, pro- thrombotic, and pro-adhesive signaling. Several chronic and acute conditions, including Bcr-abl- negative myeloproliferative neoplasms (MPNs), graft-versus-host disease (GVHD), and COVID- 19 have been noted to have increased activation of the janus kinase (JAK)-signal transducer and downstream activator of transcription (STAT) pathways. Two notable inhibitors of the JAK- STAT pathway are ruxolitinib (JAK1/2…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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